The Association of High-Molecular-Weight Hyaluronic Acid (HMWHA), Alpha Lipoic Acid (ALA), Magnesium, Vitamin B6, and Vitamin D Improves Subchorionic Hematoma Resorption in Women with Threatened Miscarriage: A Pilot Clinical Study.

Background-We evaluated whether the oral intake of high-molecular-weight hyaluronic acid (HMWHA) in association with alpha lipoic acid (ALA), magnesium, vitamin B6, and vitamin D can improve the resorption of subchorionic hematoma in cases of threatened miscarriage. Methods-In this study, we enrolled 56 pregnant women with threatened miscarriage (i.e., subchorionic hematomas, pelvic pain/uterine contractions, and/or vaginal bleeding) between the 6th and the 13th week of gestation. They were treated with vaginal progesterone (200 mg/twice a day) (control group; n = 25) or vaginal progesterone plus oral 200 mg HMWHA, 100 mg ALA, 450 mg magnesium, 2.6 mg vitamin B6, and 50 mcg vitamin D (treatment group; n = 31; DAV®-HA, LoLi Pharma srl, Rome, Italy). An ultrasound scan was performed at the first visit (T0) and after 7 days (T1) and 14 days (T2) until hematoma resorption. Results-At the ultrasound scan, the treatment group showed faster resorption of the subchorionic hematoma compared with the control group, both at T1 (control group 140 (112-180), treated group 84 (40-112), p < 0.0031), and T2 (control group: 72 (48-112), treated group: 0 (0-0), p < 0.0001). Moreover, subjective symptoms, such as vaginal bleeding, abdominal pain, and uterine contractions, showed a faster decrease in the treatment group than in the control group. Conclusions-The association may more rapidly improve the resolution of threatened miscarriage and related symptoms compared to the standard local protocol.

Paternal age and perinatal outcomes: an observational study.

OBJECTIVES: The study's primary aim was to examine the relationship between paternal age and perinatal outcomes. METHODS: This study used data from two hospital birth registries to examine the association between paternal age and adverse perinatal outcomes. The sample included all live singleton births between 2010 and 2022. The primary exposure was paternal age, and the following perinatal outcomes were considered: mode of conception, mode of delivery, pregnancy complications, and neonatal outcomes. RESULTS: A total of 15,232 pregnant women were considered. Maternal and paternal ages were 31.9 ± 5.3 and 36.5 ± 6.5 years, respectively. Independent of maternal, paternal age was associated with lower odds of spontaneous conceptions (OR 0.930, 95 % CI 0.968/0.993; p=0.003) and higher odds of intracytoplasmatic sperm injection (OR 1.054, 95 % CI 1.045/1.062; p=0.0001), respectively. In contrast to maternal age, paternal age decreased the odds of any (OR 0.922, 95 % CI 0.985/0.999; p=0.032) and urgent/emergent (OR 0.984, 95 % CI 0.975/0.993; p=0.0001) cesarean delivery. Paternal age did not affect the gestation length, placental or neonatal weight, blood loss during delivery, and neonatal 5th-minute Apgar score. CONCLUSIONS: Paternal age is associated with perinatal outcomes. These findings suggest that advanced paternal age may have implications for reproductive counseling and prenatal care.

A prospective cohort study evaluating exclusive breastfeeding in late preterm infants.

BACKGROUND: Breastfeeding can be challenging in neonates born between 34 0/7 and 36 6/7 weeks gestation (late preterm). METHODS: This prospective cohort study aims to evaluate exclusive breastfeeding at discharge, at three and six months of life in late preterm infants, and to identify facilitators and challenges to it. We included late preterm neonates eligible for the rooming-in. Data about breastfeeding at discharge, at three and six months of life were collected. RESULTS: Two hundred and fourteen late preterm infants were included in the study. At discharge 70 infants (32.7%) were fed with human milk and 144 (67.2%) were not. Non-exclusive breastfeeding was more common in women who were primiparous, had hypertension, and who underwent cesarean sections. Non-exclusive breastfeeding was associated with a low birthweight (<2500 g), ≥2 blood glucose controls, weight loss >10%, and longer hospital stay. Early first latch-on and skin-to-skin contact were more frequently associated with exclusive human milk feeding (P<0.001). Late preterm neonates born at 35 weeks showed a significant increase in exclusive human milk feeding at 3 months compared to the rate at discharge (P=0.004). CONCLUSIONS: In this cohort, early first latch-on and immediate skin-to-skin contact resulted associated with exclusive human milk feeding. Despite formula-fed during hospitalization, infants born at ≥35 weeks gestation who were exclusively breastfed at follow-up increased.

Effect of Oral High Molecular Weight Hyaluronic Acid (HMWHA), Alpha Lipoic Acid (ALA), Magnesium, Vitamin B6 and Vitamin D Supplementation in Pregnant Women: A Retrospective Observational Pilot Study.

Background-Pregnancy represents a nutritional challenge, since macro- and micronutrients intake can affect mother' health and influence negative outcomes. The aim of this retrospective pilot study is to evidence whether the oral supplementation with high molecular weight hyaluronic acid (HMWHA), in association with alpha lipoic acid (ALA), magnesium, vitamin B6 and vitamin D, in pregnant women, could reduce adverse effects, such as PTB, pelvic pain, contraction and hospitalization. Methods-Data were collected from n = 200 women treated daily with oral supplements of 200 mg HMWHA, 100 mg ALA, 450 mg magnesium, 2.6 mg vitamin B6 and 50 mcg vitamin D (treatment group) and from n = 50 women taking with oral supplements of 400 mg magnesium (control group). In both groups, supplementation started from the 7th gestational week until delivery. Results-Oral treatment with HMWHA, in association with ALA, magnesium, vitamin B6 and vitamin D in pregnant women, significantly reduced adverse events, such as PTB (p < 0.01), pelvic pain and contractions (p < 0.0001), miscarriages (p < 0.05) and admission to ER/hospitalization (p < 0.0001) compared with the control group. Conclusions-Despite HMWHA having been poorly used as a food supplement in pregnant women, our results open a reassuring scenario regarding its oral administration during pregnancy.

L-Arginine supplementation in pregnancy: a systematic review of maternal and fetal outcomes.

BACKGROUND/AIM OF THE STUDY: L-Arginine (L-Arg)/Nitric Oxide (NO) system is involved in the pathophysiology of relevant Obstetric conditions. This review aims at summarizing the effects of L-Arg supplementation in pregnancy looking at safety and efficacy. METHODS: We conducted a systematic review of the literature utilizing PubMed for studies published from inception to September 2022. The search included human and animal studies where L-Arg was supplemented pre-conceptionally or during pregnancy, by either oral or intravenous route. The main perinatal outcomes were focused. RESULTS: Among 1028 publications, 51 studies were eligible for inclusion, 25 were performed in women, and the remnant in animals. Compared to controls/placebo, the supplementation with L-Arg reduced the development of pre-eclampsia (four studies), decreased blood pressure, and reduced the need for antihypertensive drugs in women with Hypertensive Disorders of Pregnancy (HDP, eight studies). In women carrying growth retarded fetuses, L-Arg improved fetoplacental circulation, birth weight and neonatal outcomes (five studies), while in the case of threatened preterm birth, L-Arg reduced uterine contractions (two studies). In several animal species, L-Arg supplementation in pregnancy improved reproductive performance by increasing the litter number and size. Moreover, in pre-eclamptic and metabolic syndrome experimental models, maternal hypertension and fetal growth were improved. CONCLUSION: L-Arg displays biological activities in pregnancies complicated by HDP and growth restriction, both in women and animal models. L-Arg administration is safe and could be a candidate as an intervention beneficial to maternal and fetal outcomes, at least in moderate clinical disorders.

Women's perception of fetal movements and perinatal outcomes: results of a prospective cohort study.

BACKGROUND: Active fetal movements (AFMs) are a sign of the well-being of the baby during pregnancy and suggests the integrity of the cardiovascular, musculoskeletal, and nervous systems of the fetus. The abnormal perception of AFMs is associated with an increased risk of adverse perinatal outcomes such as stillbirth (SB) and brain damage. Several definitions of " decreased fetal movements" have been proposed, but none of them has been universally accepted. The aim of the study is to investigate the perinatal outcomes in relation to AFMs frequency and perception in term pregnancy with an ad hoc questionnaire administered to the women before delivery. STUDY DESIGN: This was a prospective case-control study on pregnant women at term referring to the Obstetric Unit of the University Hospital of Modena, Italy, between January 2020 and March 2020. A validated questionnaire was administered to women who agreed to participate in the study. Therefore, women were subdivided into the case and control groups: cases included women who experienced adverse perinatal outcomes (APO) such as perinatal mortality (SB and early neonatal mortality), operative delivery (cesarean section or vacuum) due to fetal distress, Apgar 5' < 7, neonatal resuscitation at birth and NICU Admission, while controls were women who experienced delivery and birth without APO in the same period. RESULTS: Seventy-seven cases and 178 controls that compiled the questionnaire were included in the analysis. Characteristics significantly associated with APO were low education (OR 1.57, CI 95% 1.11-2.22), nulliparity (OR 1.76, CI 95% 1.20-2.58), obesity (OR 1.55, CI 95% 1.10-2.17), neonatal male gender (OR 1.92 CI95% 1.33-2.78) and centile at birth (< 10° and >90°) (OR 2.77, 95%CI 2.17, 3.55). There was no association between any answer about strengths, frequency and vigor of perceived fetal movements and APO. Even any maternal perception of fetal hiccups or uterine contractions wasn't associated with APO. On the other hand, women who referred to frequent change positions during sleep (OR 1.55 CI95% 1.05-2.30) and women who snore (OR 1.43 CI95% 1.01-2.05) showed a statistically significant increase of APO. CONCLUSIONS: Our data confirm the significant association between modifiable risk factors (such as obesity and low education) and APO. Thus, healthcare providers should be aware of the importance of intervention in reducing obesity, therefore snoring and related sleep apnea syndrome. Finally, changing position during sleep while not the perception of modified/reduced fetal movements significantly could induce the worst obstetric outcomes.

Healthy preterm newborns: Altered innate immunity and impaired monocyte function.

Birth prior to 37 completed weeks of gestation is referred to as preterm (PT). Premature newborns are at increased risk of developing infections as neonatal immunity is a developing structure. Monocytes, which are key players after birth, activate inflammasomes. Investigations into the identification of innate immune profiles in premature compared to full-term infants are limited. Our research includes the investigation of monocytes and NK cells, gene expression, and plasma cytokine levels to investigate any potential differences among a cohort of 68 healthy PT and full-term infants. According to high-dimensional flow cytometry, PT infants have higher proportions of CD56+/- CD16+ NK cells and immature monocytes, and lower proportions of classical monocytes. Gene expression revealed lower proportions of inflammasome activation after in vitro monocyte stimulation and the quantification of plasma cytokine levels expressed higher concentrations of alarmin S100A8. Our findings suggest that PT newborns have altered innate immunity and monocyte functional impairment, and pro-inflammatory plasmatic profile. This may explain PT infants' increased susceptibility to infectious disease and should pave the way for novel therapeutic strategies and clinical interventions.

Association of maternal Body Mass Index and parity on induced labor stages.

BACKGROUND: Obesity is a widespread pandemic and obstetric care must adapt to meet the needs of obese pregnant women. Little is known about the impact of Body Mass Index (BMI) on the induction of labor (IOL). Therefore, our objective was to evaluate if the duration of the first and second stages of IOL is affected by maternal BMI in nulliparous and multiparous women. METHODS: We included singleton pregnancies at term with cephalic presentation whose labor was induced from June 2018 to December 2019. Women were divided into two groups according to pre-pregnancy BMI in normal weight and obese women. RESULTS: A total of 668 women with IOL were included in the study, among them, 349 had a normal weight and 321 were obese. The first stage of labor was longer in obese multiparous than normal-weight women (normal weight 81.98±71.7 vs. obese 134.3±158.1 min, P=0.000), while the second stage resulted significantly shorter (normal weight 22.2±27.8 vs. obese 14.3±14.2 min, P=0.000). The total time elapsed from IOL beginning and delivery was significantly higher in obese nulliparous (normal weight 10.4±19.7 vs. obese 22.0±26.2 h, P=0.000). Operative vaginal deliveries, emergency cesarean section, and failed IOL resulted to be similar between the groups. CONCLUSIONS: Obese multiparous women have longer first stages of labor while shorter second stages. The total time for induced obese nulliparous to reach delivery is higher than the normal weight. It might be reasonable to reconsider the partographs according to maternal BMI in case of induced labor for future obstetric practice.

Nutraceuticals and polycystic ovary syndrome: a systematic review of the literature.

BackgroundThis study proposes a review of nutraceuticals used in the treatment of typical symptoms of Polycystic Ovary Syndrome (PCOS).The aim is to provide a classification of the most widely used nutraceutical supplements identifying the most effective nutraceuticals on glucose and insulin metabolism, the androgenic hormone profile, fertility, ovulatory capacity, inflammation, and oxidative stress.Material and MethodsWe included randomized controlled trials on PCOS patients undergoing administration of nutraceuticals, in particular vitamin D, vitamin E, probiotics, and inositols. These administrations are variable in terms of dosage, single supplementation, or combined with other compounds, dosage, and duration of the intervention.ResultsThe supplementation of inositols, at the physiologic ratio of 40: 1 of myo- and D-chiro-inositols, resulted to be the most effective in improving the glucose homeostasis and fertility, with a restoration of ovulatory capacity and menstrual regularity. Other nutraceuticals are particularly effective in reducing hyperandrogenism, with promising results demonstrated by the combinations of vitamin D and probiotics, vitamin E and coenzyme Q10, and the enrichment of inositol therapy with group B vitamins. An improvement in the inflammatory status and antioxidant capacity is obtained with the co-supplementation of probiotics and selenium or with vitamin E combined with omega 3.ConclusionsInositol supplementation is effective in the treatment of insulin resistance and fertility. Probiotics reduced hyperandrogenism, inflammatory and oxidative conditions, and resulted more effective when combined with selenium. Although these results proved to be satisfactory, further studies are needed with larger samples and a more homogeneous analysis of the outcomes.

Implementation of guidelines about women with previous cesarean section through educational/motivational interventions.

OBJECTIVE: To investigate the effect of a quality improvement project with an educational/motivational intervention in northern Italy on the implementation of the trial of labor after cesarean section (CS). METHOD: A pre-post study design was used. Every birth center (n = 23) of the Emilia-Romagna region was included. Gynecologist opinion leaders were first trained about Italian CS recommendations. Barriers to implementation were discussed and shared. Educational/motivational interventions were implemented. Data of multipara with previous CS, with a single, cephalic pregnancy at term, were collected during two periods, before (2012-2014) and after (2017-2019) the intervention (2015-2016). The primary outcome was the rate of vaginal birth after CS (VBAC) and perinatal outcomes. RESULTS: A total of 20 496 women were included. The VBAC rate increased from 18.1% to 23.1% after intervention (P < 0.001). The likelihood of VBAC-adjusted for age 40 years or older, Caucasian, body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) at least 30, previous vaginal delivery, and labor induction-was increased by the intervention by 42% (odds ratio 1.42, 95% confidence interval 1.31-1.54). Neonatal well-being was improved by intervention; neonates requiring resuscitation decreased from 2.1% to 1.6% (P = 0.001). CONCLUSION: Educating and motivating gynecologists toward the trial of labor after CS is worth pursuing. Health quality improvement is demonstrated by increased VBAC even improving neonatal well-being.

First-trimester prediction model for placental vascular disorders: An observational prospective study.

This study aims to develop a multivariable predictive model for the risk of placental vascular complications (PVC), by using biochemical, biophysical, anamnestic and clinical maternal features available at the first trimester. PVC include gestational hypertension, preeclampsia, placenta abruption, intrauterine growth restriction (IUGR), and stillbirth. Prospective study that included all singleton pregnancies attending the first-trimester aneuploidy screening (11 +0-12 +6 weeks) at Obstetrics Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. In a total of 503 women included in the analysis, 40 patients were in the PVC group. The final prediction model for PVC included the following independent variables: pre-pregnancy BMI ≥ 30 (OR = 2.65, 95% CI = 1.04; 6.75, p = 0.0415), increasing values of mean arterial pressure (OR = 1.06, 95% CI = 1.02; 1.10, p = 0.0008), PAPP-A < 2.40465 U/L (OR = 0.43, 95% CI = 0.19; 0.96, p = 0.0388) and decreasing values of PlGf (MoM) (OR = 0.28, 95% CI = 0.10; 0.79, p = 0.0153). The area under the ROC curve was 79.4% indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to -2.562, which corresponds to a 7.2 % probability of having PVC. By using such a cut-off, the risk of PVC can be predicted in our sample with sensitivity equal to 82,4 % and specificity equal to 69,9 %. This model for early prediction of PVC is a promising tool to early identify women at greater risk for placenta vascular complications.

Cancer screenings among sexual and gender minorities by midwives' point of view.

INTRODUCTION: Although women belonging to sexual and gender minorities are more at risk of gynecological and breast cancer, pieces of evidence have been provided that this population finds hardships getting involved in cancer screening programs. This happens because they tend to avoid clinical settings because of fear of discrimination, heteronormative assumptions, heterosexism, classism, and homophobic slurs by healthcare professionals. On the other hand, medical programs that allow healthcare providers to have experience with LGBTQ people are scarce and there are no specific tools to assess sexual cancer risks in this population. EVIDENCE ACQUISITION: Studies included were obtained searching MEDLINE with keywords "lesbians," "queer women," "trans women," "LGBTQ women," "cervical cancer screening," "pap test," "oncology screening," "mammogram" and "prevention." Furthermore, 1577 papers were found. After filtering for species, sex, language, and time range, 820 papers were left. The number of works included was 24 after title screening and 20 after abstract screening and full-text screening. EVIDENCE SYNTHESIS: More research will be needed to develop tools with an inclusive, non-judgmental, and open language capable of engaging the LGBTQ community. Cancer screening programs involve a large variety of healthcare providers including midwives. CONCLUSIONS: Midwives are multifaceted healthcare professionals whose large competence spectrum includes a variety of knowledge and skills going from antenatal care to education and research and they may efficiently provide cancer screenings. Midwives have been asking for more specialistic roles and calling for specific instruction to face the complex and ever-changing reality.

Fetal head malposition and epidural analgesia in labor: a case-control study.

BACKGROUND: The fetal head malposition in labor leads to prolonged labor, cesarean delivery and increased perinatal morbidity. Epidural analgesia has been associated with fetal head malposition, but it remains unknown if this relation is causal. OBJECTIVE: To compare the incidence of fetal malposition during labor and maternal/fetal outcomes, between women who received epidural analgesia with those who did not use the analgesic method. STUDY DESIGN: Case control study including 500 women with a single fetus in vertex position who gave birth at term at the Policlinic Hospital of Modena between May 2019 and July 2019. Two-hundred and fifty women belonged to the epidural analgesia (EA) group and 250 to the control group. RESULTS: The rate of posterior occiput positions occurred 4 times more frequently in the EA group than in the control group (8.8% vs 2.2%, p = .004). Cesarean sections were significantly higher in the EA group (11.6% vs 1.6%, p < .0000) as well as the need for augmentation with oxytocin (20% vs 8%, p = .0001) compared to the control group, in which spontaneous delivery prevailed instead. Women with epidural had labors that lasted on average 7.0 h against the 3.30 h of controls (p < .0000). The length of 2nd stage of labor was 55 vs 30 min (p = .009), respectively. No differences in blood loss and Apgar score between groups. Early breastfeeding was significantly higher among controls (82% vs 92.8%, p = .0004). CONCLUSIONS: Women receiving epidural analgesia in labor have higher rate of fetal malposition, prolonged labors, and more cesarean sections than controls. However, further studies are required to confirm a causal association between EA and fetal head malposition.

First trimester metabolomics 1H-NMR study of the urinary profile predicts gestational diabetes mellitus development in obese women.

OBJECTIVE: Obesity is one of the main risk factors for the development gestational diabetes mellitus (GDM). Thus, we aim to identify changes in the urinary metabolomics profile of obese women at first trimester of pregnancy in order to predict later GDM diagnosis. RESEARCH DESIGN AND METHODS: In this nested case-control study, urine samples collected in the first trimester of pregnancy obtained from obese women who developed GDM (n = 29) and obese women who did not develop diabetes (n = 25 NO GDM) were analyzed with Nuclear Magnetic Resonance spectroscopy combined with Multivariate Statistical Analysis. GDM diagnosis was obtained with one-step oral glucose load. RESULTS: OPLS-DA significantly separated the GDM women from NO GDM women. Specifically, GDM women were characterized by a higher level of tryptophan, trigonelline, hippurate, and threonine, and lower levels of 1-methylnicotinamide, 3-hydroxykynurenine, glycocholate, isoleucine, kynurenine, and valine compared to NO GDM women. CONCLUSION: In a prevalently Caucasian population, the changes of some metabolites such as tryptophan, trigonelline, and branch-chained amino acids in the urinary profile of obese women in the first trimester are able to make unequivocal prediction of those which later test positive for GDM. This approach could be useful to diagnose much earlier obese women with GDM allowing lifestyle counselling and other interventions.

Carboplatin-paclitaxel in triple-negative metastatic breast cancer during pregnancy with neoplastic thrombosis.

The treatment of breast cancer (BC) diagnosed during pregnancy is a challenging situation for the patient, family and healthcare providers. Here we describe the case of a 35-year-old woman diagnosed with a triple-negative breast cancer relapse during pregnancy. She previously underwent neoadjuvant chemotherapy without any response, subsequent left skin sparing mastectomy plus axillary node dissection and radiation therapy to the chest wall and supraclavicular lymph nodes. Two years later, during her first single pregnancy, the patient presented a subclavian vein thrombosis and a BC relapse to locoregional lymph nodes. At 24 weeks of gestation, a first line treatment with weekly paclitaxel and carboplatin was started. Considering the disease progression after two complete cycles of chemotherapy, the patient had an elective caesarean section at 32+6 weeks. A full-body CT-scan and a PET-scan after the delivery showed a massive neoplastic thrombosis involving the left jugular, brachiocephalic and internal mammary vein, as well the superior vena cava and the right atrium. Few data are available on platinum-based chemotherapy during pregnancy in BC patients. Nevertheless, the choice of therapy was conditioned by the previous absence of response to anthracycline and taxane. In case of BC diagnosis during pregnancy, a multidisciplinary management as in the case described is recommended to increase the chance of survival both for the patients and their babies.

Vertebral artery dissection in term pregnancy after cervical spine manipulation: a case report and review the literature.

BACKGROUND: Vertebral artery dissection is an uncommon, but potentially fatal, vascular event. This case aimed to describe the pathogenesis and clinical presentation of vertebral artery dissection in a term pregnant patient. Moreover, we focused on the differential diagnosis, reviewing the available evidence. CASE PRESENTATION: A 39-year-old Caucasian woman presented at 38 + 4 weeks of gestation with a short-term history of vertigo, nausea, and vomiting. Symptoms appeared a few days after cervical spine manipulation by an osteopathic specialist. Urgent magnetic resonance imaging of the head was obtained and revealed an ischemic lesion of the right posterolateral portion of the brain bulb. A subsequent computed tomography angiographic scan of the head and neck showed a right vertebral artery dissection. Based on the correlation of the neurological manifestations and imaging findings, a diagnosis of vertebral artery dissection was established. The patient started low-dose acetylsalicylic acid and prophylactic enoxaparin following an urgent cesarean section. CONCLUSION: Vertebral artery dissection is a rare but potential cause of neurologic impairments in pregnancy and during the postpartum period. It should be considered in the differential diagnosis for women who present with headache and/or vertigo. Women with a history of migraines, hypertension, or autoimmune disorders in pregnancy are at higher risk, as well as following cervical spine manipulations. Prompt diagnosis and management of vertebral artery dissection are essential to ensure favorable outcomes.

Treatment of menopausal symptoms: concomitant modification of cortisol.

OBJECTIVES: To evaluate whether change in menopausal symptoms is related to modification of 24-hour urinary cortisol. METHODS: Sixty-nine postmenopausal women were treated for their menopausal symptoms with either estrogen progestin therapy (0.3 mg conjugate equine estrogens and 1.5 mg medroxyprogesterone acetate; n = 25), phytoestrogens (75 mg isoflavones, twice daily; n = 21) or acupuncture (once a week; n = 23). Baseline and treatment-induced changes of total and subscale scores (vasomotor, depression, anxiety, somatization, sexuality) of the Greene's Climacteric Scale and of 24-hour urinary cortisol were evaluated. RESULTS: At baseline, 24-hour urinary cortisol was related to Greene's Climacteric Scale score (P < 0.0001). Independent determinants (R2 = 0.319) were the Greene's subscales scores of depression (with a mean difference of 24-h cortisol for score unit expressed as beta coefficient of regression (b) of 4.91, 95% CI 2.14-7.7; P = 0.0007), and of somatization (b 3.04 95% CI 0.69-5.4; P = 0.012). The Greene's Climacteric Scale score (-5.67 ±â€Š6.8; P = 0.0001) and 24-hour cortisol (-23.6 ±â€Š45.7 µg/24 h; P = 0.0001) declined after 3 months of treatment. Changes of 24-hour cortisol values were linearly related to changes of total Greene's Climacteric Scale score with a mean change for unit score (b) of 2.10, 95% CI 0.47-3.73; P = 0.012). CONCLUSIONS: Present data indicate that greater reduction in menopausal symptoms is associated with a larger decrease in cortisol levels. Possible implication of this finding on the long-term consequences for women's health needs to be explored.